Simultaneously achieving tight glucose control and other treatment targets in diabetes reduces the risk of kidney complications, researchers found.

Action Points

Note that the study treatment aimed to reach American Diabetes Association-recommended goals through an aggressive education and medication intervention.

Simultaneously achieving tight glucose control and other targets in diabetes reduces the risk of kidney complications, researchers found.

An aggressive multifactorial intervention appeared to delay diabetic nephropathy better when more targets were achieved (P=0.002 for trend) in a longitudinal study of Chinese patients led by Ming-Chia Hsieh, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan.

The risk of new-onset microalbuminaria dropped 27.1% for those who met the American Diabetes Association-recommended goal of less than 7% glycosylated hemoglobin (P=0.03), the researchers reported in the Jan. 25 Archives of Internal Medicine.

Reaching the systolic blood pressure goal of less than 130 mm Hg reduced this risk 35.5% (P=0.002). Achieving the HDL cholesterol goal -- over 50 mg/dL for women and 40 mg/dL for men -- reduced the risk by 28.5% (P=0.02).

"The control of microalbuminuria may halt progress to overt nephropathy and reduce occurrence of cardiovascular events in these patients," Hsieh's group wrote.

They suggested that this type of intensive intervention "can be used at the very early stages of diabetic renal disease."

Prior studies had suggested that intensive therapy could prevent nephropathy in patients who had already started showing signs of progression.

So to see if starting earlier would be as effective, Hsieh and colleagues initiated a longitudinal cohort study of 1,290 patients with type 2 diabetes and normoalbuminuria in which participants received intensified treatment to meet ADA-recommended goals on glucose, blood pressure, cholesterol, and triglycerides.

To this end, patients got the combined efforts of a physician, nurse, and dietitian working together on counseling and patient education to modify behavior.

By the end of the intervention patients were more likely to have switched from single agent glucose-lowering treatment to insulin plus an oral hypoglycemic agent and to have gone on an antihypertensive (74% versus 48% baseline), statin (58.1% versus 28.0% baseline), and fibrate (14.0% versus 3.0% baseline).

By the end of the study period, the mean glycosylated hemoglobin was 7.3%, while blood pressure averaged 129.3/74.4 mm Hg. Mean LDL cholesterol was 98.6 mg/dL, triglycerides were at 116.0 mg/dL, and mean HDL cholesterol was 53.6 mg/dL.

Over the 4.5 years of follow-up, 16.4% of patients developed new-onset microalbuminuria.

Unlike attainment of HDL cholesterol, glycosylated hemoglobin, and systolic blood pressure goals, reaching those for LDL cholesterol, diastolic blood pressure, and triglycerides appeared to have little impact on kidney function.

But the more targets patients reached, the less likely they were to develop microalbuminuria (P=0.002).

The majority of participants in the study reached one or two of the treatment targets (71.4%) and 8.1% achieved three.

Those who did reach two or three of the goals were at significantly lower risk of new-onset microalbuminuria than the 20.5% who didn't reach any of the goals (P<0.001).

Those who reached one target tended to be at lower risk as well, but the effect was not significant compared with reaching none of the goals (P=0.35).

One of the concerns with the tight glucose control goal has been hypoglycemia. In the study, 217 patients had at least one episode. Four cases involved major hypoglycemia, though without clinical morbidity or mortality.

Overall, 37 patients died from any cause during the study period.

A review of recent large trials of aggressive glycemic control -- U.K. Prospective Diabetes Study (UKPDS) and the U.S.-based ACCORD, ADVANCE, and VA Diabetes trials -- suggested a two- to threefold increased risk of severe hypoglycemia without macrovascular benefits.

In the recent ACCORD trial, tight glucose control that brought hemoglobin A1c close to 6%, with a target of less than the standard 7.0%, resulted in 22% excess mortality risk.

The search for a reason behind this risk has yet to turn up a culprit. Analyses have suggested that hypoglycemia isn't to blame and that the lower A1c levels themselves aren't a problem.

In the wake of the negative findings from ACCORD, ADVANCE, and the VA trials, leading diabetologists had suggested that pushing too hard in people who couldn't reach the targets might have been at fault.

Rather than a one-size-fits all approach, the ADA guidelines suggest individualizing treatment targets.

Hsieh's group acknowledged that "even with close attention, not all our patients could achieve the ADA-recommended goals," but re-emphasized that for patients who could achieve targets, there were benefits.

The researchers cautioned that their study was limited by lack of a comparison group, no data on genetic factors, and use of potentially arbitrary treatment target cutoff points.

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